Molecular imaging techniques are among the most powerful tools for non-invasive investigation of disease and fundamental biological processes in vivo and are therefore of high significance to the mission of the NIH. Positron Emission Tomography (PET) provides sensitivity to molecular tracer concentrations several orders of magnitude less than any other imaging technique offering a large fundamental sensitivity advantage. Also PET is able to produce rigorous quantitative 3D uptake distribution uniquely free of attenuation and scatter effects giving it another strong advantage over other methods such as optical imaging. Since mouse is by far the most popular species in molecular imaging, high resolution is of exceptional importance. A number of commercial scintillator based dedicated small animal PET scanners are on the market but are limited to a useful volumetric imaging resolution of no better than 5 [unreadable]l and are very costly ($500,000 - $850,000). Recent attempts to reduce crystal size to levels needed to improve resolution performance have shown that depth of interaction (DOI) error reduces improvement to marginal levels despite substantial cost increase demonstrating the futility of the approach. Development of a low cost, high resolution PET scanner is proposed based on revolutionary detector elements composed of lead walled straws (LWS). Compared to scintillation crystal detectors, this technology is intrinsically many fold less expensive to produce and because the position of each detected gamma ray is located precisely in 3D space, fundamentally superior camera configurations can be employed to great advantage. Detectors can be placed very close to the imaged subject and events accepted over a substantially larger solid angle providing unparalleled sensitivity while maintaining immunity from resolution degradation caused by DOI. Unlike crystal devices with DOI problems, resolution performance of LWS devices scales precisely with detector dimension. Based on scaling of performance achieved in a 4 mm straw pilot device backed up by a comprehensive Monte Carlo study an optimally designed 2 mm LWS camera can reach at least a volumetric resolution of 1.2 [unreadable]l and with recently demonstrated resolution refinements should achieve a further reduction to 0.58 [unreadable]l. Furthermore using a very small detector module count of 28, a 4 fold increase in sensitivity and throughput can be achieved. In stark contrast to crystal devices the LWS camera design produces highly uniform sensitivity and resolution over its entire very large field of view. Feasibility will be demonstrated by construction of two densely packed 200 straw LWS modules of 30 - 50 cm length. Imaging performance using a rotating gantry will be evaluated through phantom testing. Lower cost combined with quantum improvement in quality will afford an exceptional new molecular imaging tool. [unreadable] [unreadable] [unreadable]